Guzman N J, Fang M Z, Tang S S, Ingelfinger J R, Garg L C
Department of Pharmacology, University of Florida College of Medicine, Gainesville, USA.
J Clin Invest. 1995 May;95(5):2083-8. doi: 10.1172/JCI117895.
An inducible nitric oxide synthase has recently been described in proximal tubule epithelium. To investigate the effects of proximal tubule NO on Na+/K(+)-ATPase, we induced NO production in mouse proximal tubule epithelial cells by treatment with lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) followed by determinations of ouabain-sensitive ATPase activity. Na+/K(+)-ATPase activity decreased after 4 h of LPS/IFN gamma treatment, reaching maximal inhibition after 24 h (34% reduction in activity). The inhibition of Na+/K(+)-ATPase activity by LPS/IFN gamma was prevented by simultaneous incubation with N omega-nitro L-arginine and markedly blunted by removal of L-arginine from the medium. The NO donors sodium nitroprusside and SIN-1 also inhibited Na+/K(+)-ATPase activity to a similar extent than LPS/IFN gamma. However, treatment with 8-pCPT-cGMP only modestly reduced Na+/K(+)-ATPase activity. Interestingly, superoxide dismutase prevented the inhibitory effects of NO on Na+/K(+)-ATPase activity, suggesting a role for peroxynitrite in this inhibition. We conclude that NO generated by mouse proximal tubule epithelial cell iNOS inhibits Na/K ATPase activity in an autocrine fashion and that this inhibition is accompanied by a reduction in Na-dependent solute transport.
最近在近端肾小管上皮细胞中发现了一种诱导型一氧化氮合酶。为了研究近端肾小管一氧化氮对钠钾ATP酶的影响，我们通过用脂多糖（LPS）和干扰素-γ（IFNγ）处理来诱导小鼠近端肾小管上皮细胞产生一氧化氮，随后测定哇巴因敏感的ATP酶活性。LPS/IFNγ处理4小时后，钠钾ATP酶活性降低，24小时后达到最大抑制（活性降低34%）。同时与Nω-硝基-L-精氨酸孵育可防止LPS/IFNγ对钠钾ATP酶活性的抑制，而从培养基中去除L-精氨酸则可显著减弱这种抑制作用。一氧化氮供体硝普钠和SIN-1对钠钾ATP酶活性的抑制程度与LPS/IFNγ相似。然而，用8-pCPT-cGMP处理仅适度降低了钠钾ATP酶活性。有趣的是，超氧化物歧化酶可防止一氧化氮对钠钾ATP酶活性的抑制作用，表明过氧亚硝酸盐在这种抑制作用中起作用。我们得出结论，小鼠近端肾小管上皮细胞诱导型一氧化氮合酶产生的一氧化氮以自分泌方式抑制钠钾ATP酶活性，并且这种抑制伴随着钠依赖性溶质转运的减少。
